Kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury.

OBJECTIVE: To investigate the kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury (ALI). DESIGN: Prospective observational cross-over study. SETTING: Intensive care unit of a university hospital. PATIENTS: Twelve mechanically ventilated patients with ALI. INTERVENTIONS: Mechanical ventilation was transiently changed from a lung protective setting with PEEP of 15 cmH(2)O and a V(T) of 5 ml/kg predicted body weight to a more conventional ventilatory setting with PEEP of 5 cmH(2)O and V(T) of 12 ml/kg predicted body weight for a period of 6 h. MEASUREMENTS AND RESULTS: We examined the profile of interleukin (IL)-1beta, IL-1 receptor antagonist, IL-6, IL-10, and tumor necrosis factor in the plasma of all patients, and in the bronchoalveolar lavage (mini-BAL) fluid of six of these patients. Measurements were performed at baseline, 1 h, and 6 h after each change of the ventilatory setting. Switching to conventional mechanical ventilation was associated with a higher PaO(2) ( P < 0.05) and a marked increase ( P < 0.05) of measured plasma cytokines in patients with and without mini-BAL with a maximum after 1 h. Similarly, intraalveolar cytokine concentrations increased with conventional mechanical ventilation. While plasma cytokine levels returned to baseline values, intraalveolar cytokine concentrations further increased when lung protective mechanical ventilation was reestablished. CONCLUSIONS: In patients with ALI, initiation of low PEEP and high V(T) mechanical ventilation is associated with cytokine release into circulation which occurred within 1 h. It is independent from BAL procedures and can be reversed by reinstitution of lung protective mechanical ventilation.

Prolonged awakening and pulmonary edema after general anesthesia and naphazoline application in an infant.

IMPLICATIONS: Naphazoline intoxication by intrabronchial overdose caused prolonged unconsciousness of an 18-mo-old child after general anesthesia for tracheal rigid bronchoscopy. The leading symptoms were side effects involving the cardiovascular, pulmonary, and central nervous systems. Intensive care unit admission with the need for mechanical ventilation was necessary. Recovery was uneventful.

Gene variants of the bactericidal/permeability increasing protein and lipopolysaccharide binding protein in sepsis patients: gender-specific genetic predisposition to sepsis.

OBJECTIVES: To determine whether the genotype frequencies of the five bi-allelic polymorphisms in the bactericidal/permeability increasing protein (BPI) (Lys216 --> Glu; PstI polymorphism in intron 5; silent mutation G545 --> C) and the lipopolysaccharide binding protein (LBP) (Cys98 --> Gly; Pro436 --> Leu) are associated with the incidence and lethality of sepsis. DESIGN: Case control study of patients with sepsis. SETTING: Intensive care units within university hospitals. PATIENTS: A total of 204 patients diagnosed with sepsis and 250 healthy blood donors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Short DNA fragments containing the polymorphic sites of the LBP and BPI locus were amplified by the polymerase chain reaction or mismatched polymerase chain reaction. The individual polymorphisms were determined with the appropriate restriction enzyme digestions and subsequent agarose gel electrophoresis. The presence of LBP genotypes with the less frequent Gly98 allele was found to be associated with sepsis (p < .02) in male patients, but not in females. Patients which were homozygote for either of the rare Gly98 (n = 6) and/or Leu436 (n = 5) LBP alleles, furthermore, exclusively were nonsurvivors of sepsis. The genotype frequencies in the BPI gene did not differ between patients and control individuals. CONCLUSIONS: Our findings suggest that common polymorphisms in the gene for LBP in combination with male gender are associated with an increased risk for the development of sepsis and, furthermore, may be linked to an unfavorable outcome. These data support the important immunomodulatory role of LBP in Gram-negative sepsis and suggest that genetic testing may be helpful for the identification of patients with an unfavorable response to Gram-negative infection.

Effects of mechanical ventilation on release of cytokines into systemic circulation in patients with normal pulmonary function.

BACKGROUND: Mechanical ventilation with high tidal volumes (V(T)) in contrast to mechanical ventilation with low V(T) has been shown to increase plasma levels of proinflammatory and antiinflammatory mediators in patients with acute lung injury. The authors hypothesized that, in patients without previous lung injury, a conventional potentially injurious ventilatory strategy with high V(T) and zero end-expiratory pressure (ZEEP) will not cause a cytokine release into systemic circulation. METHODS: A total of 39 patients with American Society of Anesthesiologists physical status I-II and without signs of systemic infection scheduled for elective surgery with general anesthesia were randomized to receive mechanical ventilation with either (1) V(T) = 15 ml/kg ideal body weight on ZEEP, (2) V(T) = 6 ml/kg ideal body weight on ZEEP, or (3) V(T) = 6 ml/kg ideal body weight on positive end-expiratory pressure of 10 cm H2O. Plasma levels of proinflammatory and antiinflammatory mediators tumor necrosis factor, interleukin (IL)-6, IL-10, and IL-1 receptor antagonist were determined before and 1 h after the initiation of mechanical ventilation. RESULTS: Plasma levels of all cytokines remained low in all settings. IL-6, tumor necrosis factor, and IL-1 receptor antagonist did not change significantly after 1 h of mechanical ventilation. IL-10 was below the detection limit (10 pg/ml) in 35 of 39 patients. There were no differences between groups. CONCLUSIONS: Initiation of mechanical ventilation for 1 h in patients without previous lung injury caused no consistent changes in plasma levels of studied mediators. Mechanical ventilation with high V(T) on ZEEP did not result in higher cytokine levels compared with lung-protective ventilatory strategies. Previous lunge damage seems to be mandatory to cause an increase in plasma cytokines after 1 h of high V(T) mechanical ventilation.

The common functional C(-159)T polymorphism within the promoter region of the lipopolysaccharide receptor CD14 is not associated with sepsis development or mortality.

Sepsis is characterised by a systemic inflammatory response to bacterial products during infection, which interestingly both in humans and animal models is gender associated with a higher susceptibility of males than females. The CD14 receptor is involved in activation of cells by lipopolysaccharides released from Gram-negative bacteria and, as recently shown, also by products of Gram-positive bacteria (e.g., peptidoglycans and lipoteichoic acid). The functional relevance of a C(-159)T CD14 polymorphism recently has been shown based on correlation of the T allele to higher plasma levels of soluble CD14, and higher membrane expression on monocytes. We, therefore, now analysed this CD14 polymorphism in 204 patients with severe sepsis and 247 controls. No significant difference of allele frequencies was observed between sepsis patients and controls neither for males nor females. Mortality also was not associated with the polymorphism studied. This may suggest that other mechanisms for lipopolysaccharide recognition, such as the recently described Toll-like receptors are important for inflammatory cell activation in sepsis.